Xenotransplantation: swine virus in donor heart – virus infection caused patient death after two months

Transplant successful, patient still dead: In the first transplant of a pig heart into a human, the patient survived only two months. Doctors could now have found the reason for this: The problem wasn’t the donor heart itself, but a pig virus that had been transmitted undetected. This destroyed the organ and probably led to the death of the patient. The sad thing about it: The virus could have been detected with more precise detection methods.

It was a sensation – and was considered an important breakthrough in transplantation medicine: On January 7, 2022, a US patient with heart disease received a pig heart as a donor organ for the first time – it was the first successful xenotransplantation. In order to prevent rejection, ten genes had previously been modified in the donor pig, and in fact the healing initially went well. A month later, however, complications arose and the 57-year-old patient died on March 8, 2022 for initially unclear reasons.

Donor pig infected with porcine cytomegalovirus

Now the doctors could have found an explanation for this: The pig was apparently infected with the porcine cytomegalovirus (PCMV), a form of the herpes virus, as reported by senior surgeon Bartley Griffith from the University of Maryland. These swine viruses then got into the patient undetected with the donor organ and could have triggered subsequent complications.

Although the porcine cytomegalovirus is harmless to humans, it attacks pig tissue – and thus also the transplanted donor heart. Because the patient had also received strong immune-inhibiting medication to prevent rejection, the virus was able to spread almost unhindered in the pig’s heart and destroy the tissue. Previous studies in monkeys have already shown that PCMV infection greatly shortens survival after xenotransplantation.

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Detection method not sensitive enough

This is precisely the case that has long raised concerns about xenotransplantations – the transmission of foreign viruses. In order to prevent this, nose swabs were carried out on the pig before the donor organ was removed in order to test for common swine viruses. However, these tests remained negative even though the pig was infected with the cytomegalovirus.

The probable reason: “Like any herpes virus, PCMV/PRV can enter a so-called latency period and is then difficult to detect,” explains Joachim Denner, head of the working group on virus safety in xenotransplantation at Freie Universität Berlin. Because the virus hardly multiplies in this phase, the viral load is so low that it slips below the detection limit for many test methods.

However, there are methods that can still detect such a latent virus, including PCR tests of blood or tissue samples. “The transmission of PCMV/PRV could have been prevented if the detection strategies available in Germany had been used,” stresses Denner. However, these methods were apparently not used in Baltimore.

Has xenotransplantation failed as a result?

But what does this mean for xenotransplantation? Has this method, celebrated as the future of transplantation, failed? Not necessarily: the absence of rejection reactions against the alien heart shows that the genetic modifications carried out in the donor pig beforehand were effective and that the patient’s immune system did not immediately attack the pig heart modified in this way.

According to experts, xenotransplantation itself has been successful. “Despite this viral complication, which, as far as is known, unfortunately had fatal consequences, these two months of survival after the first pig heart transplant are important progress towards xenotransplantation,” comments Christine Falk, head of the Institute for Transplantation Immunology at the Hannover Medical School (MHH). .

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In her opinion, it therefore makes sense to continue to pursue xenotransplantation as an alternative – with correspondingly improved test methods against swine viruses. “There is no doubt that work will continue worldwide to one day relieve the blatant lack of donor organs with pig organs and to enable seriously ill people to donate organs to save their lives and thus extend their precious lives,” says Falk.

Quelle: Science Media Center, University of Maryland

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